Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing.

An orchestrated wound healing program drives skin repair via collective epidermal cell proliferation and migration. However, the molecular determinants of the tissue microenvironment supporting wound healing remain poorly understood. Herein we discover that proteoglycan Agrin is enriched within the early wound-microenvironment and is indispensable for efficient healing.

ELKS1 controls mast cell degranulation by regulating the transcription of Stxbp2 and Syntaxin 4 via Kdm2b stabilization.

ELKS1 is a protein with proposed roles in regulated exocytosis in neurons and nuclear factor κB (NF-κB) signaling in cancer cells. However, how these two potential roles come together under physiological settings remain unknown. Since both regulated exocytosis and NF-κB signaling are determinants of mast cell (MC) functions, we generated mice lacking ELKS1 in connective tissue MCs (-Cre) and found that while ELKS1 is dispensable for NF-κB-mediated cytokine production, it is essential for MC degranulation both in vivo and in vitro.

Association between Petal Form Variation and -like Genotype in a Hybrid Line of .

This study used three-dimensional (3D) micro-computed tomography (μCT) imaging to examine petal form variation in a hybrid cross of between a cultivar with actinomorphic flowers and a variety with zygomorphic flowers. The major objectives were to determine the genotype-phenotype associations between the petal form variation and -like alleles in . () and to morphologically investigate the differences in petal types between actinomorphic and zygomorphic flowers.

Quantifying floral shape variation in 3D using microcomputed tomography: a case study of a hybrid line between actinomorphic and zygomorphic flowers.

The quantification of floral shape variations is difficult because flower structures are both diverse and complex. Traditionally, floral shape variations are quantified using the qualitative and linear measurements of two-dimensional (2D) images. The 2D images cannot adequately describe flower structures, and thus lead to unsatisfactory discrimination of the flower shape.

Dual role of VAMP8 in regulating insulin exocytosis and islet β cell growth.

Optimal insulin secretion required to maintain glucose homeostasis is the summation of total pancreatic islet β cell mass and intrinsic secretory capacity of individual β cells, which are regulated by distinct mechanisms that could be amplified by glucagon-like-peptide-1 (GLP-1). Because of these actions of GLP-1 on islet β cells, GLP-1 has been deployed to treat diabetes. We employed SNARE protein VAMP8-null mice to demonstrate that VAMP8 mediates insulin granule recruitment to the plasma membrane, which partly accounts for GLP-1 potentiation of glucose-stimulated insulin secretion.

VAMP8/endobrevin is a critical factor for the homotypic granule growth in pancreatic acinar cells.

The delivery of newly-formed secretory content to the granule inventory occurs through direct fusion of recently formed granules and mature granules. The introduction of knockout mice allowed us to investigate the characteristics of the delivery process and to determine the core protein machinery required for granule growth. The SNARE machinery mediates membrane fusion and is essential for the granule lifecycle.

[The protective effects of SB203580 against mortality and radiation induced intestinal injury of mice].

This study is to investigate the protective effects of the SB203580 against radiation induced mortality and intestinal injury of mice. A total of 67 male C57BL/6 mice (20.0-22.

Enhanced energy expenditure, glucose utilization, and insulin sensitivity in VAMP8 null mice.

Objective: Previous studies have demonstrated that the VAMP8 protein plays a complex role in the control of granule secretion, transport vesicle trafficking, phagocytosis, and endocytosis. The present study was aimed to investigate the role of VAMP8 in mediating GLUT4 trafficking and therefore insulin action in mice.

Research Design And Methods: Physiological parameters were measured using Oxymax indirect calorimetry system in 12-week-old VAMP8 null mice.

A role for VAMP8/endobrevin in surface deployment of the water channel aquaporin 2.

Vesicle-associated-membrane protein 8 (VAMP8) is highly expressed in the kidney, but the exact physiological and molecular functions executed by this v-SNARE protein in nephrons remain elusive. Here, we show that the depletion of VAMP8 in mice resulted in hydronephrosis. Furthermore, the level of the vasopressin-responsive water channel aquaporin 2 (AQP2) was increased by three- to fivefold in VAMP8-null mice.

A role for endobrevin/VAMP8 in CTL lytic granule exocytosis.

CTL clear virus-infected cells and tumorigenic cells by releasing potent cytotoxic enzymes stored in preformed lytic granules. The exocytosis process includes polarization of lytic granules toward the immunological synapse, tethering of lytic granules to the plasma membrane and finally fusion of lytic granules with the plasma membrane to release cytotoxic enzymes. Although much is known about the molecular machineries necessary for the earlier steps in lytic granule exocytosis, the molecular machinery governing the final step in the fusion process has not been identified.

Caspases regulate VAMP-8 expression and phagocytosis in dendritic cells.

During an inflammation and upon encountering pathogens, immature dendritic cells (DC) undergo a maturation process to become highly efficient in presenting antigens. This transition from immature to mature state is accompanied by various physiological, functional and morphological changes including reduction of caspase activity and inhibition of phagocytosis in the mature DC. Caspases are cysteine proteases which play essential roles in apoptosis, necrosis and inflammation.

VAMP8 is essential in anaphylatoxin-induced degranulation, TNF-alpha secretion, peritonitis, and systemic inflammation.

VAMP8, a member of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) family of fusion proteins, initially characterized in endosomal and endosomal-lysosomal fusion, may also function in regulated exocytosis. VAMP8 physiological function in inflammation has not been elucidated. In this paper, we show that deficiency of VAMP8 protects mice from anaphylatoxin (C5a)-induced neutropenia, peritonitis, and systemic inflammation.

[Effect of selenium-protein polysaccharide extracted from Se-rich Cordyceps militaris on tumor-bearing mice].

Objective: To extract and analysis the active components of Se-protein polysaccharide from Se-rich Cordyceps militaris, and to discuss the anti-tumor effect of Se-protein polysaccharide.

Method: Protein, polysaccharides and selenium content were determined by the methods of Folin-phenol reagent (lowry), phenol-sulfate and DAN fluorescence, respectively. Tumor-bearing mouse model was established and divided into the model group, cyclophosphamide group, cordyceps high and low dosage group (200, 100 mg x kg(-1)).

VAMP8 is the v-SNARE that mediates basolateral exocytosis in a mouse model of alcoholic pancreatitis.

In rodents and humans, alcohol exposure has been shown to predispose the pancreas to cholinergic or viral induction of pancreatitis. We previously developed a rodent model in which exposure to an ethanol (EtOH) diet, followed by carbachol (Cch) stimulation, redirects exocytosis from the apical to the basolateral plasma membrane of acinar cells, resulting in ectopic zymogen enzyme activation and pancreatitis. This redirection of exocytosis involves a soluble NSF attachment receptor (SNARE) complex consisting of syntaxin-4 and synapse-associated protein of 23 kDa (SNAP-23).

Vesicle-associated membrane protein-8/endobrevin negatively regulates phagocytosis of bacteria in dendritic cells.

Phagocytosis is a specialized mechanism used by mammalian cells, particularly the cells of the immune system, such as dendritic cells (DC) and macrophages, to protect the host against infection. The process involves a complex cascade of pathways, from the ligation of surface receptors of phagocytes with components of the microorganism's surface, formation of phagosomes and subsequently phagolysosomes, to the eventual presentation of foreign Ags. Vesicle-associated membrane protein (VAMP)-8/endobrevin has been shown previously to function in the endocytic pathways.

VAMP-8 segregates mast cell-preformed mediator exocytosis from cytokine trafficking pathways.

Inflammatory responses by mast cells are characterized by massive exocytosis of prestored granular mediators followed by cytokine/chemokine release. The vesicular trafficking mechanisms involved remain poorly understood. Vesicular-associated membrane protein-8 (VAMP-8), a member of the soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE) family of fusion proteins initially characterized in endosomal and endosomal-lysosomal fusion, may also function in regulated exocytosis.

VAMP8/endobrevin as a general vesicular SNARE for regulated exocytosis of the exocrine system.

The molecular mechanism governing the regulated secretion of most exocrine tissues remains elusive, although VAMP8/endobrevin has recently been shown to be the major vesicular SNARE (v-SNARE) of zymogen granules of pancreatic exocrine acinar cells. In this article, we have characterized the role of VAMP8 in the entire exocrine system. Immunohistochemical studies showed that VAMP8 is expressed in all examined exocrine tissues such as salivary glands, lacrimal (tear) glands, sweat glands, sebaceous glands, mammary glands, and the prostate.

Endobrevin/VAMP-8 is the primary v-SNARE for the platelet release reaction.

Platelet secretion is critical to hemostasis. Release of granular cargo is mediated by soluble NSF attachment protein receptors (SNAREs), but despite consensus on t-SNAREs usage, it is unclear which Vesicle Associated Membrane Protein (VAMPs: synaptobrevin/VAMP-2, cellubrevin/VAMP-3, TI-VAMP/VAMP-7, and endobrevin/VAMP-8) is required. We demonstrate that VAMP-8 is required for release from dense core granules, alpha granules, and lysosomes.

Mouse lymphomas caused by an intron-splicing donor site deletion of the FasL gene.

A spontaneous lymphoma was detected in mice, which was caused by a recessive autosomal mutation. The genetic basis was revealed to be a 5-bp deletion at the splicing donor site of the first intron of the FasL gene, resulting in aberrant transcripts coding for non-functional proteins. This mutation of the FasL gene caused development of lymphoma in all four mouse genetic backgrounds tested and the lymphoma was characterized by an expansion of leucocytes that were TCR+CD3+B220+CD19-CD4-CD8-.

A role of VAMP8/endobrevin in regulated exocytosis of pancreatic acinar cells.

Despite our general understanding that members of the SNARE superfamily participate in diverse intracellular docking/fusion events, the physiological role of the majority of SNAREs in the intact organism remains elusive. In this study, through targeted gene knockout in mice, we establish that VAMP8/endobrevin is a major player in regulated exocytosis of the exocrine pancreas. VAMP8 is enriched on the membrane of zymogen granules and exists in a complex with syntaxin 4 and SNAP-23.

NK-2 class homeobox genes and pharyngeal/oral patterning: Nkx2-3 is required for salivary gland and tooth morphogenesis.

Head development in vertebrates requires reciprocal patterning interactions between cranial neural crest and the ectodermal, mesodermal and endodermal components of the branchial arches. Patterning elements within the pharyngeal endoderm and oral ectoderm appear to play defining roles in this process. Several homeobox genes of the NK-2 class (Nkx2-1, Nkx2-3, Nkx2-5 and Nkx2-6) are expressed regionally in the developing pharynx, and Nkx2-1 mutants and Nkx2-5/Nkx2-6 double mutants show loss of thyroid and distal lung progenitors, and pharyngeal cell viability, respectively.